Project description:Regular endurance exercise training induces beneficial functional and health effects in human skeletal muscle. The putative contribution to the training response of the epigenome as a mediator between genes and environment has not been clarified. Here we investigated the contribution of DNA methylation and associated transcriptomic changes in a well-controlled human intervention study. Training effects were mirrored by significant alterations in DNA methylation and gene expression in regions with a homogeneous muscle energetics and remodeling ontology. Differential DNA methylation predominantly occurred in regulatory enhancer regions, where known binding motifs of MRF, MEF2 and ETS proteins were identified. A transcriptional network analysis revealed modules harboring distinct ontologies, and interestingly the overall direction of the changes of methylation within each module was inversely correlated to expression changes. In conclusion, we show that highly consistent and associated modifications in methylation and expression, concordant with observed health-enhancing phenotypic adaptations, are induced by a physiological stimulus. DNA samples from vastus lateralis muscle bisopsies were included in the study. Specifically, 23 subjects performed three months of supervised endurance training. Biospies were taken at rest, before and after training. DNA methylation levels were profiled using Illumina 450K arrays.
Project description:A transcriptional map of the impact of endurance exercise training on skeletal muscle phenotype (resting muscle after endurance training)
Project description:This SuperSeries is composed of the following subset Series: GSE18583: Baseline skeletal muscle gene expression GSE35659: A transcriptional map of the impact of endurance exercise training on skeletal muscle phenotype (resting muscle after endurance training) Refer to individual Series
Project description:The molecular pathways which are activated and contribute to physiological remodeling of skeletal muscle in response to endurance exercise have not been fully characterized. We previously reported that ~800 gene transcripts are regulated following 6 weeks of supervised endurance training in young sedentary males, referred to as the training responsive transcriptome (TRT). Here we utilized this database together with data on biological variation in muscle adaptation to aerobic endurance training in both humans and a novel out-bred rodent model to study the potential regulatory molecules that coordinate this complex network of genes. We identified three DNA sequences representing RUNX1, SOX9, and PAX3 transcription factor binding sites as over-represented in the TRT. In turn, miRNA profiling indicated that several miRNAs targeting RUNX1, SOX9 and PAX3 were down-regulated by endurance training. The TRT was then examined by contrasting subjects who demonstrated the least vs. the greatest improvement in aerobic capacity (low vs. high responders), and at least 100 of the 800 TRT genes were differentially regulated, thus suggesting regulation of these genes may be important for improving aerobic capacity. In high responders, pro-angiogenic and tissue developmental networks emerged as key candidates for coordinating tissue aerobic adaptation. Beyond RNA level validation there were several DNA variants that associated with VO(2)max trainability in the HERITAGE Family Study but these did not pass conservative Bonferroni adjustment. In addition, in a rat model selected across 10 generations for high aerobic training responsiveness, we found that both the TRT and a homologous subset of the human high responder genes were regulated to a greater degree in high responder rodent skeletal muscle. This analysis provides a comprehensive map of the transcriptomic features important for aerobic exercise-induced improvements in maximal oxygen consumption. This data is from skeletal muscle post 6 weeks of endurance exercise training.
Project description:Regular endurance exercise training induces beneficial functional and health effects in human skeletal muscle. The putative contribution to the training response of the epigenome as a mediator between genes and environment has not been clarified. Here we investigated the contribution of DNA methylation and associated transcriptomic changes in a well-controlled human intervention study. Training effects were mirrored by significant alterations in DNA methylation and gene expression in regions with a homogeneous muscle energetics and remodeling ontology. Differential DNA methylation predominantly occurred in regulatory enhancer regions, where known binding motifs of MRF, MEF2 and ETS proteins were identified. A transcriptional network analysis revealed modules harboring distinct ontologies, and interestingly the overall direction of the changes of methylation within each module was inversely correlated to expression changes. In conclusion, we show that highly consistent and associated modifications in methylation and expression, concordant with observed health-enhancing phenotypic adaptations, are induced by a physiological stimulus.
Project description:Short RNA sequncing was performed to determine the effects of endurance exercise training on miRNA expression in human skeletal muscle.
Project description:Combining resistance and endurance exercises in a training regime (concurrent training) can impair improvements in muscle hypertrophy, strength, and power compared to resistance training alone. Here we aimed to characterize skeletal muscle transcriptomic changes following chronic concurrent training to determine whether contraction-induced gene expression may reveal molecular underpinnings explaining impaired adaptations. Eighteen young, healthy male participants underwent 12 weeks of resistance, endurance, or concurrent training. Maximal strength, aerobic capacity, and anaerobic power were assessed. Transcriptomics were performed on skeletal muscle biopsies obtained pre and post-intervention. Improvements to maximal anaerobic power are impaired with concurrent and endurance training. Gene expression related to plasma membrane structures was enriched while gene expression related to regulation of mRNA processing and protein degradation was suppressed with concurrent training. Considerable overlap of gene expression related to extracellular matrix remodeling was observed between concurrent and endurance training. Our results provide the first comprehensive comparison of unique and overlapping gene sets enriched following chronic resistance, endurance, and concurrent training, and reveals pathways that may have implications in relation to impaired adaptations when undertaking concurrent training.
Project description:We used gene microarray analysis to compare the global expression profile of genes involved in adaptation to exercise training in skeletal muscle from chronically strength/resistance trained (ST), endurance trained (ET) and untrained control subjects (Con). Resting skeletal muscle samples (~100mg) were obtained from the vastus lateralis of 20 subjects (Con n=7, ET n=7, ST n=6; trained groups >8 years specific training). Total RNA was extracted from tissue and microarrays completed, with test samples compared with standard human reference RNA. Subjects were characterised by performance measures of maximal oxygen uptake (VO2max) on a cycle ergometer and maximal concentric and eccentric leg strength on an isokinetic dynamometer. 263 genes were differentially expressed in trained (TR collectively ET + ST) subjects compared with Con (P<0.05) while 21 genes were different between ST and ET (P<0.05). Manual cluster analyses revealed significant regulation of genes involved in muscle structure and development in TR subjects compared with Con (P<0.05), and expression of these correlated significantly with measures of performance (P<0.05). ET had increased and ST decreased expression of gene clusters related to mitochondrial/oxidative capacity (P<0.05), and these mitochondrial gene clusters correlated significantly with VO2max (P<0.05). VO2max also correlated with expression of gene clusters that regulate fat and carbohydrate oxidation (P<0.05). We have demonstrated that chronic training has marked effects on basal gene expression by regulating levels of multiple mRNAs that transcribe genes for important functional groups in human skeletal muscle. Some specific gene clusters are expressed regardless of the training stimulus, whereas others exhibit divergent expression patterns as a result of specific training stimuli. Keywords: Comparative, cluster analysis, endurance training, strength training, muscle phenotype This was a crossectional study examining basal gene expression profiles of the human vastus lateralis. Twenty healthy males volunteered for this investigation. Seven were endurance trained cyclists (ET), who had been participating in endurance training for 8 yr. These subjects had no history of resistance training. Six subjects were strength trained power-lifters (ST) who had been participating exclusively in strength/resistance training for 9 yr. The final seven subjects were healthy controls (CON) that did not participate in any formal exercise. The study was approved by the Human Research Ethics Committee of RMIT University and Monash University Standing Committee on Ethics Research on Humans. After RNA extraction, amplification and indirect labelling, a dual colour micro-array analysis was conducted by hybridizing a test (muscle RNA; Cy5) sample and a reference (Universal human RNA; Cy3) sample on the AGRF glass slide human 8K micro-array. After data capture with the Genepix scanner and associated software data was normalised and the three populations compared using GeneSpring and simplified cluster analysis.
Project description:Analysis of skeletal muscle DNA methylation from type 2 diabetic volunteers before and after 16 weeks of chronic exercise training (two groups, one undergoing aerobic excercise and the other resistance training exercise) A biopsy was collected from the right Vastus Lateralis under local anaesthesia andGenomic DNA was extracted from 5-10 mg muscle, Bisulphite conversion (Illumina) was checked using methylation specific PCR. 4 ?l of bisulphite-converted DNA was used for hybridization on Infinium Human Methylation 450 BeadChip (Illumina)